Best practice guidelines for idiopathic nephrotic syndrome: recommendations versus reality

Andrea Pasini, Gabriella Aceto, Anita Ammenti, Gianluigi Ardissino, Vitalba Azzolina, Alberto Bettinelli, Elena Cama, Sante Cantatore, Antonella Crisafi, Giovanni Conti, Maria D'Agostino, Alessandra Dozza, Alberto Edefonti, Carmelo Fede, Elena Groppali, Chiara Gualeni, Alessandra Lavacchini, Marta Lepore, Silvio Maringhini, Paola Mariotti, Marco Materassi, Francesca Mencarelli, Giovanni Messina, Amata Negri, Marina Piepoli, Fiammetta Ravaglia, Angela Simoni, Laura Spagnoletta, Giovanni Montini, NefroKid Study Group, Andrea Pasini, Francesca Mencarelli, Chiara DeMutiis, Elena Monti, Giovanni Montini, Gabriella Aceto, Giovanni Messina, Laura Spagnoletta, Mario Giordano, Tommaso De Palo, Alberto Edefonti, Luciana Ghio, Gianluigi Ardissino, Elena Groppali, Marta Lepore, Silvio Maringhini, Vitalba Azzolina, Carmelo Fede, Roberto Chimenz, Giovanni Conti, Marco Materassi, Fiammetta Ravaglia, Maria D'Agostino, Sante Cantatore, Anita Ammenti, Chiara Gualeni, Elena Cama, Desenzano del Garda, Mariotti Paola, Amata Negri, Alberto Bettinelli, Alessandra Lavacchini, Alessandra Dozza, Ospedale Maggiore, Angela Simoni, Marina Piepoli, Felice Sica, Gabriele Ripanti Ripanti, Marina Mi lani, Paola Tommasi, Carla Romanello, Manuela Pasini, Paola Mastinu, Laura Luti, Antonella Amendolea, Silvia Manfredi, Emanuela Lanfranchi, Maria Principi, Agrippino Reciputo, Cinisello Balsamo, Marialuisa Casciana, Antonio Pellegatta, Nicola Altamura, Sesto San Giovanni, Lorena Ruzza Ruzza, Stefano Sardini, Burlo Garofalo, Claudio Ruberto, Antonella Crisafi, Reggio Emilia, Andrea Zucchini, Laura Serra, Peter Bertamini, Rita Bini, Patrizia Cortesi, Caterina Balducci, Francesca Simoni, Patrizia Fonduli, Franca Paola Zurrida, Laura De Petris, Ascoli Piceno, Vinicio Goj, Gian Luigi Marsiglia, Patrizia Caruso, Filippo Salvini, Paola Perotti, Anna Bussolini, Stefano Poli, Barbara Balduzzi, Barbara Roman, Sergio Mariani, Laura Cafarelli, Vittorio Venturoli, Andrea Corsini, Luca Casadio, Fabrizio Pugliese, Andrea Pasini, Gabriella Aceto, Anita Ammenti, Gianluigi Ardissino, Vitalba Azzolina, Alberto Bettinelli, Elena Cama, Sante Cantatore, Antonella Crisafi, Giovanni Conti, Maria D'Agostino, Alessandra Dozza, Alberto Edefonti, Carmelo Fede, Elena Groppali, Chiara Gualeni, Alessandra Lavacchini, Marta Lepore, Silvio Maringhini, Paola Mariotti, Marco Materassi, Francesca Mencarelli, Giovanni Messina, Amata Negri, Marina Piepoli, Fiammetta Ravaglia, Angela Simoni, Laura Spagnoletta, Giovanni Montini, NefroKid Study Group, Andrea Pasini, Francesca Mencarelli, Chiara DeMutiis, Elena Monti, Giovanni Montini, Gabriella Aceto, Giovanni Messina, Laura Spagnoletta, Mario Giordano, Tommaso De Palo, Alberto Edefonti, Luciana Ghio, Gianluigi Ardissino, Elena Groppali, Marta Lepore, Silvio Maringhini, Vitalba Azzolina, Carmelo Fede, Roberto Chimenz, Giovanni Conti, Marco Materassi, Fiammetta Ravaglia, Maria D'Agostino, Sante Cantatore, Anita Ammenti, Chiara Gualeni, Elena Cama, Desenzano del Garda, Mariotti Paola, Amata Negri, Alberto Bettinelli, Alessandra Lavacchini, Alessandra Dozza, Ospedale Maggiore, Angela Simoni, Marina Piepoli, Felice Sica, Gabriele Ripanti Ripanti, Marina Mi lani, Paola Tommasi, Carla Romanello, Manuela Pasini, Paola Mastinu, Laura Luti, Antonella Amendolea, Silvia Manfredi, Emanuela Lanfranchi, Maria Principi, Agrippino Reciputo, Cinisello Balsamo, Marialuisa Casciana, Antonio Pellegatta, Nicola Altamura, Sesto San Giovanni, Lorena Ruzza Ruzza, Stefano Sardini, Burlo Garofalo, Claudio Ruberto, Antonella Crisafi, Reggio Emilia, Andrea Zucchini, Laura Serra, Peter Bertamini, Rita Bini, Patrizia Cortesi, Caterina Balducci, Francesca Simoni, Patrizia Fonduli, Franca Paola Zurrida, Laura De Petris, Ascoli Piceno, Vinicio Goj, Gian Luigi Marsiglia, Patrizia Caruso, Filippo Salvini, Paola Perotti, Anna Bussolini, Stefano Poli, Barbara Balduzzi, Barbara Roman, Sergio Mariani, Laura Cafarelli, Vittorio Venturoli, Andrea Corsini, Luca Casadio, Fabrizio Pugliese

Abstract

Background: The optimal therapeutic regimen for managing childhood idiopathic nephrotic syndrome (INS) is still under debate. We have evaluated the choice of steroid regimen and of symptomatic treatment adopted by pediatricians and pediatric nephrologists in a large number of centers as the first step towards establishing a shared protocol

Methods: This was a multicenter, retrospective study. A total of 231 children (132 admitted to pediatric units) aged 6 months to <15 years who presented with onset of nephrotic syndrome to 54 pediatric units and six pediatric nephrology units in Italy between 2007 and 2009 were eligible for entry into the study.

Results: Median steroid dosing was 55 (range 27-75) mg/m(2)/day. The overall median cumulative dose regimen for the first episode was 3,440 (1,904-6,035) mg/m(2), and the median duration of the therapeutic regimen was 21 (9-48) weeks. The total duration and cumulative steroid dose were significantly higher in patients treated by pediatricians than in those treated by pediatric nephrologists (p = 0.001 and p = 0.008). Among the patient cohort, 55, 64 and 22 % received albumin infusions, diuretics and acetyl salicylic acid treatment, respectively, but the laboratory and clinical data did not differ between children treated or not treated with symptomatic drugs. Albumin and diuretic use did not vary between patients in pediatric units and those in pediatric nephrology units.

Conclusions: This study shows major differences in steroid and symptomatic treatment of nephrotic syndrome by pediatricians and pediatric nephrologists. As these differences can influence the efficacy of the treatments and the appearance of side-effects, shared guidelines and their implementation through widespread educational activities are necessary.

Trial registration: ClinicalTrials.gov NCT01386957.

Figures

Fig. 1
Fig. 1
Flowchart of the 231 enrolled pediatric patients
Fig. 2
Fig. 2
Treatment regimen for the first episode. a, b Duration (a) and total prednisone dose utilized (b) for the total patient cohort. c–f Comparison of the duration (c, d) and total prednisone dose (e, f) of the steroid regimen for the first episode used by participating pediatricians (c, e) and pediatric nephrologists (d, f). Y-axis shows the number of patients. PDN Prednisone

References

    1. McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM. Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol. 2001;16:1040–1044. doi: 10.1007/s004670100021.
    1. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003;362:629–639. doi: 10.1016/S0140-6736(03)14184-0.
    1. El Bakkali L, Rodrigues Pereira R, Kuik DJ, Ket JC, van Wijk JA. Nephrotic syndrome in The Netherlands: a population-based cohort study and a review of the literature. Pediatr Nephrol. 2011;26:1241–1246. doi: 10.1007/s00467-011-1851-8.
    1. Tarshish P, Tobin JN, Bernstein J, Edelmann CMJ. Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in children. J Am Soc Nephrol. 1997;8:769–776.
    1. Hodson EM, Knight JF, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2000;4:CD001533.
    1. Arneil GC. The nephrotic syndrome. Pediatr Clin North Am. 1971;18:547–559.
    1. Ueda N, Chihara M, Kawaguchi S, Niinomi Y, Nonoda T, Matsumoto J, Ohnishi M, Yasaki T. Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome. J Pediatr. 1988;112:122–126. doi: 10.1016/S0022-3476(88)80136-7.
    1. Ksiazek J, Wyszynska T. Short versus long initial prednisone treatment in steroid-sensitive nephrotic syndrome in children. Acta Pediatr. 1995;84:889–893. doi: 10.1111/j.1651-2227.1995.tb13787.x.
    1. Ehrich JH, Brodehl J. Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft fur Padiatrische Nephrologie. Eur J Pediatr. 1993;152:357–361. doi: 10.1007/BF01956754.
    1. Bagga A, Hari P, Srivastava RN. Prolonged versus standard initial prednisolone treatment for idiopathic nephrotic syndrome. Pediatr Nephrol. 1999;13:824–827. doi: 10.1007/s004670050708.
    1. Arbeitsgemeinschaft für Pädiatrische Nephrologie Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Lancet. 1988;1:380–383.
    1. Haute Autorité de Santé (2008) Syndrome néphrotique idiopathique de l’enfant. Service des affections de longue durée et accords conventionnels 1–22. Available at:
    1. Bagga A, Ali U, Banerjee S, Kanitkar M, Phadke KD, Senguttuvan P, Sethi S, Shah M. Management of steroid sensitive nephrotic syndrome: revised guidelines. Indian Pediatr. 2008;45:203–214.
    1. Lombel RM, Gipson DS, Hodson EMP. Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol. 2013;28:415–426. doi: 10.1007/s00467-012-2310-x.
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group KDIGO clinical practice guideline for Glomerulonephritis. Kidney Int Suppl. 2012;2:139–274. doi: 10.1038/kisup.2012.9.
    1. Wu HM, Tang JL, Sha ZH, Cao L, Li YP. Interventions for preventing infection in nephrotic syndrome. Cochrane Database Syst Rev. 2004;2:CD003964.
    1. Kayali F, Najjar R, Aswad F, Matta F, Stein PD. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med. 2008;121:226–230. doi: 10.1016/j.amjmed.2007.08.042.
    1. Kapur G, Valentini RP, Imam AA, Mattoo TK. Treatment of severe edema in children with nephrotic syndrome with diuretics alone—a prospective study. Clin J Am Soc Nephrol. 2009;4:907–913. doi: 10.2215/CJN.04390808.
    1. Monagle P, Chan AK, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Göttl U, Vesely SK, American College of Chest Physicians Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th edn: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e737S–801S. doi: 10.1378/chest.11-2308.
    1. Tabel Y, Mungan I, Karakurt C, Kocak G, Gungor S. Is edema in minimal change disease of childhood really hypovolemic? Int Urol Nephrol. 2008;40:757–761. doi: 10.1007/s11255-008-9344-9.
    1. Fliser D, Zurbrüggen I, Mutschler E, Bischoff I, Nussberger J, Franek E, Ritz E. Coadministration of albumin and furosemide in patients with the nephrotic syndrome. Kidney Int. 1999;55:629–634. doi: 10.1046/j.1523-1755.1999.00298.x.
    1. Ghafari A, Mehdizadeh A, Alavi-Darazam I, Rahimi E, Kargar C. Co-administration of albumin-furosemide in patients with the nephritic syndrome. Saudi J Kidney Dis Transplant. 2011;22:471–475.
    1. Dorhout Mees EJ. Does it make sense to administer albumin to the patient with nephrotic edema? Nephrol Dial Transplant. 1996;11:1224–1226. doi: 10.1093/ndt/11.7.1224.
    1. Rothenberg MB, Heymann W. The incidence of the nephrotic syndrome in children. Pediatrics. 1957;19:446–452.
    1. Wong W. Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after 12-month follow-up: Results of a 3-year national surveillance study. J Paediatr Child Health. 2007;43:337–341. doi: 10.1111/j.1440-1754.2007.01077.x.
    1. Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, Wigfall D, Miles P, Powell L, Lin JJ, Trachtman H, Greenbaum LA. Management of childhood onset nephrotic syndrome. Pediatrics. 2009;24:747–757. doi: 10.1542/peds.2008-1559.
    1. Feber J, Al-Matrafi J, Farhadi E, Vaillancourt R, Wolfish N. Prednisone dosing per body weight or body surface area in children with nephrotic syndrome: is it equivalent? Pediatr Nephrol. 2009;24:1027–1031. doi: 10.1007/s00467-008-1089-2.
    1. Teeninga N, Kist-van Holthe JE, van Rijswijk N, de Mos NI, Hop WC, Wetzels JF, van der Heijden AJ, Nauta J. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol. 2013;24:149–159. doi: 10.1681/ASN.2012070646.
    1. MacHardy N, Miles PV, Massengill SF, Smoyer WE, Mahan JD, Greenbaum L, Massie S, Yao L, Nagaraj S, Lin JJ, Wigfall D, Trachtman H, Hu Y, Gipson DS. Management patterns of childhood-onset nephrotic syndrome. Pediatr Nephrol. 2009;24:2193–2201. doi: 10.1007/s00467-009-1282-y.
    1. Samuel S, Morgan CJ, Bitzan M, Mammen C, Dart AB, Manns BJ, Alexander RT, Erickson RL, Grisaru S, Wade AW, Blydt-Hansen T, Feber J, Arora S, Licht C, Zappitelli M. Substantial practice variation exists in the management of childhood nephrotic syndrome. Pediatr Nephrol. 2013;28:2289–2298. doi: 10.1007/s00467-013-2546-0.
    1. Hodson E. The management of idiopathic nephrotic syndrome in children. Paediatr Drugs. 2003;5:335–349. doi: 10.2165/00128072-200305050-00006.
    1. Koomans HA, Geers AB, Dorhout Mees EJ, Kortlandt W. Lowered tissue-fluid oncotic pressure protects the blood volume in the nephrotic syndrome. Nephron. 1986;42:317–322. doi: 10.1159/000183695.
    1. Doucet A, Favre G, Deschênes G. Molecular mechanism of edema formation in nephrotic syndrome: therapeutic implications. Pediatr Nephrol. 2007;22:1983–1990. doi: 10.1007/s00467-007-0521-3.
    1. Deschenes G, Feraille E, Doucet A. Mechanisms of edema in nephrotic syndrome: old theories and new ideas. Nephrol Dial Transplant. 2003;18:454–456. doi: 10.1093/ndt/18.3.454.
    1. Smith DE, Hyneck ML, Berardi RR, Port FK. Urinary protein binding, kinetics, and dynamics of furosemide in nephrotic patients. J Pharm Sci. 1985;74:603–607. doi: 10.1002/jps.2600740604.
    1. Haws RM, Baum M. Efficacy of albumin and diuretic therapy in children with nephrotic syndrome. Pediatrics. 1993;91:1142–1146.
    1. Donckerwolcke RA, France A, Raes A, Vande Walle J. Distal nephron sodium-potassium exchange in children with nephrotic syndrome. Clin Nephrol. 2003;59:259–266. doi: 10.5414/CNP59259.
    1. Yoshimura A, Ideura T, Iwasaki S, Taira T, Koshikawa S. Aggravation of minimal change nephrotic syndrome by administration of human albumin. Clin Nephrol. 1992;37:109–114.
    1. Chalasani N, Gorski JC, Horlander JC, Craven R, Hoen H, Maya J, Brater DC. Effects of albumin/furosemide mixtures on responses to furosemide in hypoalbuminemic patients. J Am Soc Nephrol. 2001;12:1010–1016.
    1. Bircan Z, Kervancioğlu M, Katar S, Vitrinel A. Does albumin and furosemide therapy affect plasma volume in nephrotic children? Pediatr Nephrol. 2001;16:497–499. doi: 10.1007/s004670100576.
    1. Dharmaraj R, Hari P, Bagga A. Randomized cross-over trial comparing albumin and frusemide infusions in nephrotic syndrome. Pediatr Nephrol. 2009;24:775–782. doi: 10.1007/s00467-008-1062-0.
    1. Siddall EC, Radhakrishnan J. The pathophysiology of edema formation in the nephrotic syndrome. Kidney Int. 2012;82:635–642. doi: 10.1038/ki.2012.180.
    1. Rondon-Berrios H. New insights into the pathophysiology of edema in nephrotic syndrome. Nefrol. 2011;31:148–154.
    1. Deschênes G, Wittner M, Stefano A, Jounier S, Doucet A. Collecting duct is a site of sodium retention in PAN nephrosis: a rationale for amiloride therapy. J Am Soc Nephrol. 2001;12:598–601.
    1. Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int. 1985;28:429–439. doi: 10.1038/ki.1985.149.
    1. Kerlin BA, Blatt NB, Fuh B, Zhao S, Lehman A, Blanchong C, Mahan JD, Smoyer WE. Epidemiology and risk factors for thromboembolic complications of childhood nephrotic syndrome: a Midwest Pediatric Nephrology Consortium (MWPNC) study. J Pediatr. 2009;155:105–110. doi: 10.1016/j.jpeds.2009.01.070.
    1. Hoyer PF, Gonda S, Barthels M, Krohn HP, Brodehl J. Thromboembolic complications in children with nephrotic syndrome. Risk and incidence. Acta Paediatr Scand. 1986;75:804–810. doi: 10.1111/j.1651-2227.1986.tb10294.x.
    1. Citak A, Emre S, Sâirin A, Bilge I, Nayir A. Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol. 2000;14:138–142. doi: 10.1007/s004670050029.
    1. Glassock RJ. Prophylactic anticoagulation in nephrotic syndrome: A clinical conundrum. J Am Soc Nephrol. 2007;18:2221–2225. doi: 10.1681/ASN.2006111300.
    1. Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res. 2006;118:397–407. doi: 10.1016/j.thromres.2005.03.030.

Source: PubMed

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